Advertisement

best practice onkologie

, Volume 14, Issue 6, pp 262–271 | Cite as

Fortgeschrittene Basalzell- und Plattenepithelkarzinome der Haut

Aktuelle systemische Therapieoptionen
  • T. GambichlerEmail author
  • L. Susok
CME
  • 157 Downloads

Zusammenfassung

Nach dem Melanom ist das kutane Plattenepithelkarzinom („cutaneous squamous cell carcinoma“ [cSCC]) der am zweithäufigsten zum Tode führende Hauttumor. Ende 2017 wurden für das fortgeschrittene cSCC positive Ergebnisse zum Immuncheckpointinhibitor Cemiplimab berichtet, einem humanen, monoklonalen Antikörper gegen das Protein PD-1 („programmed death 1“). Aber auch für die primär gegen das Melanom eingesetzten PD-1-Blocker (Pembrolizumab, Nivolumab) gibt es inzwischen überzeugende Daten für die systemische cSCC-Behandlung. Das Basalzellkarzinom (BCC) ist bei Kaukasiern der häufigste Hautkrebs, der zwar selten metastasiert, aber häufiger lokal inoperabel ist. Mit der im Jahr 2012 bzw. 2015 erfolgten Zulassung der Hedgehog-Inhibitoren Vismodegib und Sonidegib besteht nun die Möglichkeit, bei metastasiertem oder inoperablem BCC eine wirkungsvolle orale zielgerichtete Systemtherapie einzusetzen. Zu den Immuncheckpointblockern beim BCC gibt es ebenfalls erste vielversprechende Daten.

Schlüsselwörter

Epitheliale Neoplasien Monoklonale Antikörper „Programmed Cell Death 1 Receptor“ Hedgehog-Inhibitoren· Cetuximab 

Advanced basal and squamous cell carcinomas of the skin

Current systemic treatment options

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most fatal skin tumor after melanoma. Positive results in advanced cSCC were reported at the end of 2017 for the immune checkpoint inhibitor cemiplimab, a human monoclonal antibody against the programmed cell death protein 1 (PD-1). However, convincing data for PD-1 blockers (pembrolizumab, nivolumab), which are primarily used for melanoma, are now available for the systemic treatment of cSCC as well. Basal cell carcinoma (BCC) is the most common form of skin cancer in Caucasians. Although it rarely metastasizes, it is more often locally inoperable. The approval of the hedgehog inhibitors vismodegib and sonidegib in 2012 and 2015, respectively, has made it possible to use effective oral targeted systemic therapy for metastatic or inoperable BCC. The first promising data on immune checkpoint blockers in BCC are also available.

Keywords

Neoplasms, epithelial Antibodies, monoclonal Programmed cell death 1 receptor Hedgehog-inhibitors· Cetuximab 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

Gemäß der Richtlinien des Springer Medizin Verlags werden Autoren und Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben.

Autoren

T. Gambichler: A. Finanzielle Interessen: Expertenmeetings und Vorträge: MSD, BMS, Roche, Novartis, Sanofi, Janssen – B. Nichtfinanzielle Interessen: Angestellter Dermatologe, Klinik für Dermatologie der Ruhr-Universität Bochum, Bochum. L. Susok: A. Finanzielle Interessen: Vorträge und Advisory Boards: BMS, Novartis, Roche, FOMF, UCB Pharma, Celgene, Sunpass – B. Nichtfinanzielle Interessen: Angestellte Dermatologin, St. Josef-Hospital Bochum, Ruhr-Universität Bochum.

Wissenschaftliche Leitung

Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme.

Der Verlag

erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
    Koelblinger P, Lang R (2018) New developments in the treatment of basal cell carcinoma: Update on current and emerging treatment options with a focus on vismodegib. Onco Targets Ther 11:8327–8340PubMedPubMedCentralGoogle Scholar
  2. 2.
    Lang et al (2018) Basalzellkarzinom der Haut. https://www.awmf.org/leitlinien/detail/ll/032-021.html . Zugegriffen: 21. Januar 2019
  3. 3.
    Waldman A, Schmults C (2019) Cutaneous squamous cell carcinoma. Hematol Oncol Clin North Am 33(1):1–12PubMedGoogle Scholar
  4. 4.
    Siegel R et al (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30.  https://doi.org/10.3322/caac.21387 PubMedGoogle Scholar
  5. 5.
    Burton KA et al (2016) Cutaneous squamous cell carcinoma: A review of high-risk and metastatic disease. Am J Clin Dermatol 17:491–508.  https://doi.org/10.1007/s40257-016-0207 PubMedGoogle Scholar
  6. 6.
    Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, Broeders N, del Marmol V, Chatelet V, Dompmartin V, Kessler M, Serra A, Hofbauer G, Pouteil-Noble C, Campistol J, Kanitakis J, Roux A, Decullier E, Dantal J et al (2012) Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 367:329–339PubMedGoogle Scholar
  7. 7.
    Parikh SA, Patel VA, Raatner D (2014) Advances in the management of cutaneous squamous cell carcinoma. F1000prime Rep 6:70PubMedPubMedCentralGoogle Scholar
  8. 8.
    Murad A, Ratner D (2001) Cutaneous squamous-cell carcinoma. N Engl J Med 344(13):975–983Google Scholar
  9. 9.
    Breuninger et al (2013) Plattenepithelkarzinom der Haut. https://www.awmf.org/leitlinien/detail/ll/032-022.html . Zugegriffen: 22. Januar 2019
  10. 10.
    Apalla Z, Lallas A, Sotiriou E et al (2017) Epidemiological trends in skin cancer. Dermatol Pract Concept 7(2):1–6PubMedPubMedCentralGoogle Scholar
  11. 11.
    Lomas A, Bee-Leonardi J, Bath-Hextall F (2012) A systematic review of worldwide incidence of non-melanoma skin cancer. Br J Dermatol 166:1069–1080PubMedGoogle Scholar
  12. 12.
    Stratigos A, Garbe C, Lebbe C et al (2015) Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer 51(14):1989–2007PubMedGoogle Scholar
  13. 13.
    Berliner JG, Schulman JM, Lazarova Z et al (2019) Response of cutaneous squamous cell carcinoma to treatment with cetuximab. Dermatol Surg 45(2):313–316PubMedGoogle Scholar
  14. 14.
    Maubec E, Petrow P, Scheer-Senyarich I et al (2011) Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 29(25):3419PubMedGoogle Scholar
  15. 15.
    Preneau S, Rio E, Brocard A, Peuvrel L, Nguyen JM, Quéreux G, Dreno B (2014) Efficacy of cetuximab in the treatment of squamous cell carcinoma. J Dermatolog Treat 25(5):424–427PubMedGoogle Scholar
  16. 16.
    Samstein RM, Ho AL, Lee NY, Barker CA (2014) Locally advanced and unresectable cutaneous squamous cell carcinoma: outcomes of concurrent cetuximab and radiotherapy. J Skin Cancer.  https://doi.org/10.1155/2014/284582 PubMedPubMedCentralGoogle Scholar
  17. 17.
    Dereure O, Missan H, Girard C, Costes V, Guillot B (2016) Efficacy and tolerance of cetuximab alone or combined with chemotherapy in locally advanced or metastatic cutaneous squamous cell carcinoma: An open study of 14 patients. Dermatology 232(6):721–730PubMedGoogle Scholar
  18. 18.
    Sadreddini S, Baradaran B, Aghebati-Maleki A, Sadreddini S, Shanehbandi D, Fotouhi A, Aghebati-Maleki L (2018) Immune checkpoint blockade opens a new way to cancer immunotherapy. J Cell Physiol 234(6):8541–8549.  https://doi.org/10.1002/jcp.27816 PubMedGoogle Scholar
  19. 19.
    Borradori L, Sutton B, Shayesteh P, Daniels GA (2016) Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: Preliminary experience in five cases. Br J Dermatol 175(6):1382–1386PubMedGoogle Scholar
  20. 20.
    Chang AL, Kim J, Luciano R, Sullivan-Chang L, Colevas AD (2016) A case report of unresectable cutaneous squamous cell carcinoma responsive to pembrolizumab, a programmed cell death protein 1 Inhibitor. JAMA Dermatol 152(1):106–108PubMedGoogle Scholar
  21. 21.
    Winkler JK, Schneiderbauer R, Bender C, Sedlaczek O, Fröhling S, Penzel R, Enk A, Hassel JC (2017) Anti-programmed cell death-1 therapy in nonmelanoma skin cancer. Br J Dermatol 176(2):498–502PubMedGoogle Scholar
  22. 22.
    Stevenson ML, Wang CQ, Abikhair M, Roudiani N, Felsen D, Krueger JG, Pavlick AC, Carucci JA (2017) Expression of programmed cell death ligand in cutaneous squamous cell carcinoma and treatment of locally advanced disease with pembrolizumab. JAMA Dermatol 153(4):299–303PubMedGoogle Scholar
  23. 23.
    Degache E, Crochet J, Simon N, Tardieu M, Trabelsi S, Moncourier M, Templier I, Foroni L, Lemoigne A, Pinel N, Gil H, Bouillet L, Leccia MT, Charles J (2018) Major response to pembrolizumab in two patients with locally advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 32(7):e257–e258PubMedGoogle Scholar
  24. 24.
    Blum V, Müller B, Hofer S, Pardo E, Zeidler K, Diebold J, Strobel K, Brand C, Aebi S, Gautschi O (2018) Nivolumab for recurrent cutaneous squamous cell carcinoma: Three cases. Eur J Dermatol 28(1):78–81PubMedGoogle Scholar
  25. 25.
    Midgen M, Rischin D, Schmults C, Guminski A, Hauschild A, Lewis K, Chung C, Hernandez-Aya L, Lim A, Chang A, Rabinowits G, Thai A, Dunn L, Hughes B, Khushalani N, Modi B, Schadendorf D, Gao B, Seebach F et al (2018) PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 379:341–351Google Scholar
  26. 26.
    Hermel DJ, Ragab OM, Higgins S, Wysong A, In GK (2018) PD-1 inhibition in cutaneous squamous cell carcinoma (cSCC). J Clin Oncol 36(15_suppl):e15100–e15100Google Scholar
  27. 27.
    Maubec E, Boubaya M, Petrow P, Basset-Seguin N, Grob JJ et al (2018) Pembrolizumab as first line therapy in patients with unresectable squamous cell carcinoma of the skin: Interim results of the phase 2 CARSKIN trial. J Clin Oncol 36(15_suppl):9534–9534Google Scholar
  28. 28.
    Kudchadkar RR, Yushak ML, Lawson DH, Delman KA, Lowe MC et al (2018) Phase II trial of pembrolizumab (MK-3475) in metastatic cutaneous squamous cell carcinoma (cSCC). J Clin Oncol 36(15_suppl):9543–9543Google Scholar
  29. 29.
    Beasley GM, Kurtz J, Vandeusen J, Howard JH, Terando A, Agnese D et al (2017) Immune checkpoint inhibitor therapy as a novel and effective therapy for aggressive cutaneous squamous-cell carcinoma. Clin Skin Cancer 1(2):75–81Google Scholar
  30. 30.
    Frampton JE, Basset-Séguin N (2018) Vismodegib: A review in advanced basal cell carcinoma. Drugs 78(11):1145–1156PubMedGoogle Scholar
  31. 31.
    Tay EY, Teoh YL, Yeo MS (2018) Hedgehog pathway inhibitors and their utility in basal cell carcinoma: A comprehensive review of current evidence. Dermatol Ther (Heidelb).  https://doi.org/10.1007/s13555-018-0277-7 Google Scholar
  32. 32.
    Xie P, Lefrançois P (2018) Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: A systematic review and meta-analysis. J Am Acad Dermatol 79(6):1089–1100.e17PubMedGoogle Scholar
  33. 33.
    Chen L, Aria AB, Silapunt S, Lee HH, Migden MR (2018) Treatment of advanced basal cell carcinoma with sonidegib: Perspective from the 30-month update of the BOLT trial. Future Oncol 14(6):515–525PubMedGoogle Scholar
  34. 34.
    Lipson EJ, Lilo MT, Ogurtsova A, Esandrio J, Xu H, Brothers P, Schollenberger M, Sharfman WH, Taube JM (2017) Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade. J Immunother Cancer 5:23PubMedPubMedCentralGoogle Scholar
  35. 35.
    Ikeda S, Goodman AM, Cohen PR, Jensen TJ, Ellison CK, Frampton G, Miller V, Patel SP, Kurzrock R (2016) Metastatic basal cell carcinoma with amplification of PD-L1: Exceptional response to anti-PD1 therapy. NPJ Genom Med 1:16037.  https://doi.org/10.1038/npjgenmed.2016.37 PubMedPubMedCentralGoogle Scholar
  36. 36.
    Falchook GS, Leidner R, Stankevich E, Piening B, Bifulco C, Lowy I, Fury MG (2016) Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer 4:70PubMedPubMedCentralGoogle Scholar
  37. 37.
    Cohen PR, Kato S, Goodman AM, Ikeda S, Kurzrock R (2017) Appearance of new cutaneous superficial basal cell carcinomas during successful nivolumab treatment of refractory metastatic disease: Implications for immunotherapy in early versus late disease. Int J Mol Sci 18(8):E1663PubMedGoogle Scholar
  38. 38.
    Cannon JGD, Russell JS, Kim J, Chang ALS (2018) A case of metastatic basal cell carcinoma treated with continuous PD-1 inhibitor exposure even after subsequent initiation of radiotherapy and surgery. JAAD Case Rep 4(3):248–250PubMedPubMedCentralGoogle Scholar
  39. 39.
    Fischer S, Ali OH, Jochum W, Kluckert T, Flatz L, Siano M (2018) Anti-PD-1 therapy leads to near-complete remission in a patient with metastatic basal cell carcinoma. Oncol Res Treat 41(6):391–394PubMedGoogle Scholar
  40. 40.
    Chang ALS, Tran DC, Cannon JGD, Li S, Jeng M, Patel R, Van der Bokke L, Pague A, Brotherton R, Rieger KE, Satpathy AT, Yost KE, Reddy S, Sarin K, Colevas AD (2018) Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study. J Am Acad Dermatol 80(2):564–566PubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Hauttumorzentrum Ruhr-Universität Bochum, Klinik für Dermatologie, Allergologie und VenerologieSt. Josef-Hospital Bochum, Ruhr-Universität BochumBochumDeutschland

Personalised recommendations